Early Satellite Cell Communication Creates a Permissive Environment for Long-Term Muscle Growth

Authors

Kevin A. Murach, University of KentuckyFollow
Bailey D. Peck, University of KentuckyFollow
Robert A. Policastro, University of Indiana
Ivan J. Vechetti Jr., University of KentuckyFollow
Douglas W. Van Pelt, University of KentuckyFollow
Cory M. Dungan, University of KentuckyFollow
Lance T. Denes, University of Florida
Xu Fu, University of Kentucky
Camille R. Brightwell, University of KentuckyFollow
Gabriel E. Zentner, University of Indiana
Esther E. Dupont-Versteegden, University of KentuckyFollow
Christopher I. Richards, University of KentuckyFollow
Jeramiah J. Smith, University of KentuckyFollow
Christopher S. Fry, University of KentuckyFollow
John J. McCarthy, University of KentuckyFollow
Charlotte A. Peterson, University of KentuckyFollow

Abstract

Using in vivo muscle stem cell (satellite cell)-specific extracellular vesicle (EV) tracking, satellite cell depletion, in vitro cell culture, and single-cell RNA sequencing, we show satellite cells communicate with other cells in skeletal muscle during mechanical overload. Early satellite cell EV communication primes the muscle milieu for proper long-term extracellular matrix (ECM) deposition and is sufficient to support sustained hypertrophy in adult mice, even in the absence of fusion to muscle fibers. Satellite cells modulate chemokine gene expression across cell types within the first few days of loading, and EV delivery of miR-206 to fibrogenic cells represses Wisp1 expression required for appropriate ECM remodeling. Late-stage communication from myogenic cells during loading is widespread but may be targeted toward endothelial cells. Satellite cells coordinate adaptation by influencing the phenotype of recipient cells, which extends our understanding of their role in muscle adaptation beyond regeneration and myonuclear donation.

Document Type

Article

Publication Date

3-28-2021

Notes/Citation Information

Published in iScience, v. 24, issue 4, 102372.

© 2021 The Authors

This is an open access article under the CC BY-NC-ND license (https://creativecommons.org/licenses/by-nc-nd/4.0/).

Digital Object Identifier (DOI)

https://doi.org/10.1016/j.isci.2021.102372

Funding Information

This work was supported by funding from the NIH National Institutes of Arthritis and Musculoskeletal and Skin Diseases (AR060701to C.A.P. and J.J.M. and AR071753 to K.A.M), National Institute on Aging (AG049086 to C.A.P. and J.J.M.and AG063994 to K.A.M), National Institute of Diabetes and Digestive and Kidney Diseases (DK119619 to C.A.P. and J.J.M), and National Institute of General Medical Sciences (GM130349 to J.J.S.).

Related Content

The accession number for the scRNA-seq data reported in this paper is GEO: GSE168872. The code to find the proportional difference in cell populations between two samples is available as an R library on GitHub: https://github.com/rpolicastro/scProportionTest/releases/tag/v1.0.0.

Supplemental information can be found online at https://doi.org/10.1016/j.isci.2021.102372. It is attached to the end of the downloaded article, and is also available for download as an additional file listed at the end of this record.

Repository Citation

Murach, Kevin A.; Peck, Bailey D.; Policastro, Robert A.; Vechetti, Ivan J. Jr.; Van Pelt, Douglas W.; Dungan, Cory M.; Denes, Lance T.; Fu, Xu; Brightwell, Camille R.; Zentner, Gabriel E.; Dupont-Versteegden, Esther E.; Richards, Christopher I.; Smith, Jeramiah J.; Fry, Christopher S.; McCarthy, John J.; and Peterson, Charlotte A., "Early Satellite Cell Communication Creates a Permissive Environment for Long-Term Muscle Growth" (2021). Center for Muscle Biology Faculty Publications. 13.
https://uknowledge.uky.edu/musclebiology_facpub/13